Over the past years there has been increasing interest in the role of prenatal and early childhood factors in influencing chronic disease risk in adulthood. In the field of cardiovascular disease (CVD), a growing body of literature has reported inverse associations between birthweight and CVD risk in adults. However, there is still debate on whether this association reflects an underlying etiologic process or is simply the result of confounding by socioeconomic status. In addition: there is little information on the mechanisms that may underlie the observed associations, on maternal factors that may be important, or on how prenatal factors may interact with later growth and with CVD risk factors in adulthood. We propose to use extensive prenatal, perinatal, and early childhood data collected as part of unique birth cohorts established approximately 40 years ago supplemented by assessments in adulthood, to investigate the early determinants of CVD risk. We will examine at total of 1000 sibling-sets who are offspring of pregnant women enrolled during 1959 to 1967 in two New England sites (Boston and Providence) of the National Collaborative Perinatal Project (NCPP) and in the Childhood Health and Development Study (CHDS). The use of a sibling-set design will enhance our ability to control for family influences. Over-sampling of sibling sets with at least one low birthweight infant will ensure sufficient power to detect low birthweight effects. Extensive prenatal, perinatal, and early childhood information will be linked to assessments in adulthood. The outcomes investigated will include blood pressure, measures of glucose tolerance, carotid distensibility and intimal-medial thickness (IMT) and heart period variability. We will (1) examine whether associations between birthweight and adult CVD risk factors persist after stringent control for SES;: (2) establish to what extent it is fetal growth, rather than birthweight per se, that is a predictor of CVD risk; (3) investigate the role maternal characteristics; and (4) examine how fetal growth interacts with childhood growth trajectories and adult body size. We will also build on previous research by examining the relation of prenatal factors not only to selected CVD risk factors, but also to outcomes which may help us begin to understand the mechanisms and physiopathologic processes linking early life experiences to cardiovascular risk in adulthood. Thus we will also examine the relation of early life factors to large artery elasticity (as assessed by carotid distensibility), to subclinical atherosclerosis (as assessed by carotid intimal-medial wall thickness (IMT)), and to heart period variability (HPV). Addressing the aims we propose will contribute to our understanding of the causes of CVD generally, and may have important policy implications.